Regulation of stem and progenitor cells in the adrenal cortex

Abstract

The adrenal cortex is an endocrine organ comprised of three histological zones, the outermost zona glomerulosa, the intermediate zona fasciculata, and the innermost zona reticularis. High plasticity of the adrenal gland is supported by pools of stem and progenitor cells that are deployed to sustain physiological and homeostatic demands. In recent decades, exciting new discoveries elucidating the identity, function, and fate of these cell populations have emerged. In this review, we describe paracrine and endocrine signaling loops that are crucial for adrenal biology, focusing on recent studies unpacking the enigmatic nature of adrenal stem and progenitor cell populations.

Keywords: Adrenal cortex; Endocrine signaling; Progenitor cells; Signaling pathways; Stem cells.

Figure 1. Molecules and signaling in adrenal homeostasis.

Schematic of spatial location of molecules and signaling pathways discussed in this review. Nestin, YAP/TAZ, Tcf21, Wt1, Gli1, and Rspo3 are expressed in the adrenal capsule. YAP/TAZ are also found expressed throughout the adrenal cortex. EZH2 expression is particularly concentrated in the transition zone from zG to zF. Shh- and Wnt4-expressing cells, along with WNT-responsive cells, primarily populate the zG. Finally, the adrenocortical WNT gradient is stronger in the outer cortex and weaker in the innermost cortex. PKA signaling, active in the zF, inhibits a zG phenotype. Androgens suppress cell recruitment from capsule.

Figure 2. Cell lineages in adult mouse adrenal.

Schematic exemplifying cell lineages of the adrenal gland. Shh-expressing cells give rise to cells of the zG that can differentiate into CYP11B2+ cells, which in turn originate zF CYP11B1+ cells. In the capsule, SF1-/Nestin+ cells can contribute to the steroidogenic cortex, particularly under stress conditions. Capsular Gli1+ cells are recruited to produce differentiated steroidogenic cells that delaminate into the cortex. This process is hindered by androgens in male mice.